tbuckley/cabot-search huggingface dataset:
Impact of body mass index (BMI) and weight changes on hematopoietic stem cell transplant (HSCT) outcomes in the elderly population.
Authors: Anshu Hemrajani, Zahra Ismail, Destry James Elms, Mary Moore, Scott E. Smith, Patrick Hagen, Patrick J. Stiff, Stephanie Tsai
Journal: Journal of Clinical Oncology (2023)

e19058 Background: HSCT remains the only curative treatment for high-risk hematologic malignancies. Reduced intensity conditioning (RIC) has increasingly allowed transplant of elderly patients. However, maximizing outcomes in this population remains a challenge. We examine the influence of BMI and weight changes on HSCT outcomes in the elderly. Methods: This was a retrospective review of 216 patients ≥60 years of age who underwent first HSCT at the Loyola University Medical Center between 8/30/2000-6/15/2017. Pearson Chi-square tests for independence evaluated the associations between categorical variables and timing of recurrence. Fisher’s exact test were used where expected frequencies were &lt;5. Independent two-sample t-tests and ANOVA assessed differences in numerical variables. Results: BMI at time of transplant, defined as underweight (BMI&lt;18), normal weight (BMI 18-25), overweight (BMI 25-30), and morbidly obese (BMI&gt;30), did not impact incidence of cardiac dysfunction, pulmonary complications (Cx’s), renal Cx’s, graft versus host disease (GVHD), paraenteral nutrition (TPN) use, changes in albumin, or mortality. However, there was a trend towards increased disease relapse in those who were not normal weight (p=.08). Normal weight (BMI 18-25) at Day 100 was associated with decreased cardiac dysfunction (p=.02), days of hospitalization (p = .03), and mortality (p = .02) compared to non-normal BMI (BMI &lt; 18 or BMI &gt; 25). But there appeared no difference in rates of renal Cx's, GVHD, TPN use, or relapse. Having &gt;10% weight change at discharge from transplant admission was associated with increased renal Cx’s (p = .007), infectious Cx’s (p = .03), use of TPN (p = .006), length of hospital stay (p = .0002), and mortality (p = .009). However, it was not associated with cardiac dysfunction, pulmonary Cx’s, readmissions by 6 months, GVHD, or relapse. Having &gt;10% weight change at Day 100 was associated with increased risk of acute (p = .01) and chronic GVHD (p = .002) and readmissions by 6 months (p = .01), but not with other Cx’s, relapse, or mortality. Conclusions: Patients who were underweight or overweight at key timepoints may impact complications and HSCT outcomes. Furthermore, maintaining a stable weight during transplant admission and the first 100 days was associated with decreased rates of complications and adverse HSCT outcomes. These findings warrant further evaluation into age-related weight and nutritional targets to improve understanding and optimize HSCT outcomes in this vulnerable population. [Table: see text]
The RAINBO MMRd-GREEN trial (GCIG/DGOG/ENGOT-EN14<sup>2</sup>): A phase III trial on the addition of adjuvant durvalumab to radiotherapy in patients with high-risk MMRd endometrial cancer.
Authors: Merve Kaya, Nanda Horeweg, Alexandra Leary, Stephen Welch, Stefan Kommoss, Nicola Weidner, Francesco Fanfani, Domenica Lorusso, John McGrane, Toon Van Gorp, Ingrid Boere, Anneke M. Westermann, Joan B. Heijns, Hein Putter, Karen Verhoeven-Adema, Vincent T.H.B.M. Smit, Carien L. Creutzberg, Tjalling Bosse, Judith R. Kroep
Journal: Journal of Clinical Oncology (2023)

TPS5633 Background: The molecular class of endometrial cancer (EC) is both prognostic and predictive in high-risk EC (HREC). The TransPORTEC research consortium showed that patients with MMRd HREC did not benefit from adjuvant chemotherapy added to radiotherapy. MMRd tumors are particularly sensitive to immunotherapy. We hypothesize that adjuvant durvalumab added to standard radiotherapy will increase recurrence-free survival (RFS) in patients with MMRd HREC. Methods: MMRd-GREEN is an international, open-label, randomized phase III trial and part of the RAINBO program (NCT05255653). Eligible patients will be allocated (1:1) to adjuvant durvalumab 1500 mg once every 4 weeks for 1 year combined with radiotherapy or standard radiotherapy alone. The primary endpoint is RFS at 3 years. Secondary endpoints are pelvic, vaginal and distant RFS, EC-specific survival, overall survival, treatment-related toxicity, health-related quality of life and exploratory translational research . Main inclusion criteria include histologically confirmed stage IB/II with (substantial) lymph-vascular space invasion (LVSI) or stage IIIA-C MMRd EC, after hysterectomy and bilateral salpingo-oophorectomy (regardless of lymphadenectomy or sentinel lymph node biopsy) without macroscopic residual disease. Molecular classification must be performed according to the WHO 2020 algorithm. The target accrual is 316 patients, accounting for a total drop-out rate of 12%. This sample size yields 80% power to detect a 13% increase in the 3-year RFS (hazard ratio 0.58) as a result of the addition of durvalumab, with an accrual duration of 48 months and follow-up period of 30 months. No interim analysis is planned; an independent data monitoring committee will routinely monitor recurrences and adverse events. Enrollment: Since August 2022, the trial is open for recruitment in the Netherlands and per February 10 th 2023, the first 3 patients have been enrolled. Activation of more international centers is ongoing. Clinical trial information: NCT05255653 .
Outcome of deep venous thrombosis and pulmonary embolism in COVID-19 cancer patients vs non-cancer patients.
Authors: Can Jones, Kristina D. Menchaca, Catherine Ostos, Mohamed Elsheshtawi, Virginia Velez-Quinones, Shachar Peles, Hayder Saeed
Journal: Journal of Clinical Oncology (2023)

e24066 Background: COVID-19 is associated with an increased incidence of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Multiple mechanisms including COVID-19-induced endothelial dysfunction, cytokine storm, complement activation, and hypoxia lead to the activation of the coagulation cascade. Of note, VTE is the most common presentation of cancer-associated thrombosis. It is associated with worsened prognosis and mortality in both COVID-19 patients and cancer patients. Some studies indicated that comparing to COVID-19 non-cancer population, COVID-19 cancer patients have a higher risk of developing VTE. Methods: This retrospective cohort study identified 1,306 adult patients admitted to the tertiary medical center for COVID-19 treatment from 2020 to 2021, including 38 active cancer patients and 1268 non-cancer patients. Skin cancers were excluded. All patients received anticoagulant for VTE prophylaxis. The primary outcome of interest was the VTE incidence. Results: There was no significant difference in baseline demographics between groups. 35 non-cancer COVID-19 patients developed DVT (2.76%), while one patient had DVT in the cancer group (2.63%); for PE, 25 non-cancer patients were found to have PE (1.97%), while one cancer patient was diagnosed with PE (2.63%). There were no statistical differences in DVT and PE incidences between the COVID-19 cancer group and the non-cancer group during hospitalization. However, the cancer group was found to have older age (P &lt; 0.001), higher D-dimer (P = 0.024) level, and more severe thrombocytopenia (P &lt; 0.001). The COVID-19 cancer group revealed significantly higher in-hospital mortality (36.84%) comparing to the non-cancer group (14.98%) (P &lt; 0.001). Conclusions: Our study revealed no differences in the incidence of PE and DVT between the COVID-19 cancer population and the COVID-19 non-cancer population; COVID-19 cancer patients experienced significantly higher mortality comparing to COVID-19 non-cancer patients. This highlights the importance of having larger-scale studies in the future to assess different outcomes in patients with malignancy and COVID-19.
Comparison of clinical outcomes in patients with advanced pulmonary sarcomatoid carcinoma treated with immunotherapy-based regimen or chemotherapy: A study based on the SEER database and multicentric real-world settings.
Authors: Duanyang Peng, Le Xiong, Yuxi Luo, Anwen Liu, Xia Wang, Zhimin Zeng
Journal: Journal of Clinical Oncology (2023)

e20573 Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare pulmonary cancer characterised by early metastasis and invasion, predominantly diagnosed with locally advanced or metastasis, hindering the possibility of surgical intervention. However, a standardised treatment strategy for advanced PSC is yet to be established. Herein, we aimed to evaluate the effects of immunotherapy-based strategies or chemotherapy on patients with advanced PSC. Methods: We conducted a retrospective study to compare the clinical outcomes of immunotherapy-based regimens and chemotherapy in patients with advanced PSC using the Surveillance, Epidemiology, and End Results (SEER) database and data from three cancer centres. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Univariate and multivariate analyses were performed to identify prognostic factors. Results: In total, 202 patients with stage IV PSC were identified from the SEER database. The median OS was 5 months. The median follow-up time of PSC patients from three cancer centres was 27.5 months Considering all three cancer centres, first-line treatment with a first-line immunotherapy-based regimen and chemotherapy were administered to 12 and 16 patients, respectively. The median PFS was 2.1 (95% confidence interval [CI] [2.1, 4.1]) and 7.2 (95% CI [6.8, 7.6]) months for the chemotherapy- and immune-based groups, respectively (p &lt; 0.001). The median OS was 3.6 (95% CI [1.6, 5.6]) and 13.7 (95% CI [5.1, 22.3]) months for the chemotherapy and immune-based groups, respectively (p = 0.003). Multivariate analysis revealed that the immunotherapy-based regimen was an independent prognostic factor for PFS and OS (p &lt; 0.01, hazard ratio [HR] = 0.22, 95% CI [0.07,0.67] and p &lt; 0.01 HR = 0.27 95% CI [0.11,0.68], respectively). Conclusions: Conventional chemotherapy has limited benefits in patients with stage IV PSC. However, patients with advanced PSC who received first-line immunotherapy-based regimens exhibited a remarkable response. The immunotherapy-based regimen was an independent prognostic factor for PFS and OS.
Real world study on the effect of PARPi as maintenance therapy after first-line and second-line chemotherapy on platinum sensitivity in patients with recurrent high-grade serous epithelial ovarian cancer.
Authors: Yanglong Guo, Yingli Zhang
Journal: Journal of Clinical Oncology (2023)

e17574 Background: This study investigated the effect of PARPi as maintenance therapy after 1st-line and 2nd-line chemotherapy on platinum sensitivity in patients with recurrent high-grade serous epithelial ovarian cancer (rHGSOC). Methods: 172 patients with rHGSOC at Zhejiang Cancer Hospital and Jiaxing Maternity and Child Health Care Hospital from Jan 2017 to Dec 2021were retrospectively analyzed. Patients who received PARPi as maintenance therapy after first-line chemotherapy were enrolled to the 1st-PARPi group (n=23), and subjects who did not receive PARPi maintenance therapy were enrolled to the 1st control group (n=105). Similarly, 2nd- PARPi group (had not use PARPi in first-line treatment n=30), 2nd-control group (n=89) were divided. To evaluate progression-free survival (PFS), the first progression to second progression (TTSP), the second progression to third progressio (TTTP), PFS between the second progression and the end of the second-line chemotherapy (PFSs), PFS between the third progression and the end of the third-line chemotherapy (PFSt) and to compare whether PARPi as maintenance therapy affects the platinum sensitivity of these patients. Results: PFSs in 1st-PARPi vs.1st-control group (median 5 vs. 11 m; p=0.0037). PFSt in 2nd-PARPi vs. 2nd-control group(median 4.5 vs. 9.0 m; p=0.0009). TTSP in 1st-PARPi vs. 1st-control group (median 11 vs. 16 m; p=0.0045). TTTP in 2nd-PARPi vs. 2nd-control group (median 10 vs. 15 m; p=0.0007). Among the 23 patients in 1st-PARPi group and 105 patients in 1st-control group, 9 and 99 patients were platinum sensitive while 14 and 6 patients were platinum resistant respectively (HR 14.46, 95% CI =4.07-51.53, P &lt; 0.0001). Among the 30 patients in 2nd-PARPi group and 89 patients in 2nd-control group, 10 and 71 patients were platinum sensitive while and 20 and 18 patients were platinum resistant respectively (HR 4.37 95% CI=1.98-9.64, P &lt; 0.0001). Age, stage, residual tumor after initial surgery treatment and the courses of platinum-based chemotherapy before PARPi,BRCA gene mutation were not the related factors affecting the platinum sensitivity of next line chemotherapy. There was no statistical difference in the effect of duration of PARPi on the platinum sensitivity of next line chemotherapy (duration of PARPi≥ 18 months vs. &lt;18 months in 1st-PARPi group, HR 0.60, 95% CI=0.18-2.04, P=0.41; duration of PARPi≥ 12 months vs. &lt;12 months in 2nd-PARPi group, HR 0.62, 95% CI=0.26-1.48, P=0.24, respectively). Conclusions: Patients with rHGSOC using PARPi affected the platinum sensitivity and were more likely to lead to platinum resistance no matter how long the during of PARPi were.This conclusion was consistent with the cross resistance between PARPi and platinum. Care should be taken when using PARPi after 1st-line and 2nd-line chemotherapy as maintenance therapy.
Genomic and transcriptomic characterization of ovarian cancer under neoadjuvant and adjuvant chemotherapy.
Authors: Ying Jin, Jiayu Chen, Yi Zhao, Yu Gu, Ying Shan, Yan Li, Wei Wang, Meng Qin, Yu Dong, Baochen Du, Lingya Pan, Han Liang
Journal: Journal of Clinical Oncology (2023)

e17571 Background: Neoadjuvant chemotherapy (NACT) has become a routine selection for late-staged ovarian cancer patients to reduce the tumor load before debulking surgery; and chemotherapy remains as the mainstream therapy for ovarian cancer. However, the effects of NACT on the cancer genome and the molecular determinates of tumor response to chemotherapy in ovarian cancer have not been characterized systematically. Methods: We obtained 121 clinical samples from 44 ovarian cancer patients (19 underwent NACT and 25 did not) and collected the key clinical features for these samples such as age, tumor stage, platinum-free interval, and platinum response. We then performed whole-exome sequencing for all the 121 samples and RNA-sequencing for 54 samples. We conducted a systematic comparative analysis between samples collected from the patients with and without NACT to characterize the effects of NACT on the cancer genome and transcriptomes. Focusing on the genomic and transcriptomic differences of treatment-naive samples between platinum sensitive and resistant patients, we also did a comparative analysis to identify molecular features that can predict the response to platinum. Results: We observed significantly elevated mutational signatures associated with platinum chemotherapy in the samples from patients who have undergone NACT. We also found increased microsatellite instability (MSI) in the post-NACT primary samples compared to treatment-naive ones. Interestingly, the prevalence of CCNE1 amplification significantly decreased in the post-NACT metastatic samples of patients. Consistently, the mRNA expression of CCNE1 appeared to down-regulated in such samples. Furthermore, the expression signature of cancer hallmarks related to this gene decreased in post-NACT metastatic samples, such as E2F targets, G2M checkpoint, and mitotic spindle. Remarkably, we found that homologous recombination deficiency (HRD) is a strong indicator for platinum sensitivity, which was also supported by HRD-associated mutational signatures. The expression signature of immune-related hallmarks was significantly upregulated in sensitive primary samples, including interferon alpha response, interferon gamma response, and IL6 JAK STAT3 signaling. Conclusions: Based on comprehensive profiling for genomic and transcriptomic characterization of a large cohort of ovarian cancer patients, we found that (i) NACT likely increased MSI and decreased prevalence of CCNE1 amplification; and (ii) a high HRD score and elevated immune-related expression signatures can strongly predict the sensitivity to platinum-based chemotherapy. These results lays a key foundation for develop novel, effective therapies for ovarian cancer.
The validity of a machine learning algorithm in predicting response to immune checkpoint inhibitors in melanoma.
Authors: Faisal Fa'ak, Nicolas Coudray, George Jour, Clara Goldberg, Paul Johannet, Alexander Chan Chi Huang, Tara Mitchell, Xiaowei Xu, Aristotelis Tsirigos, Jeffrey S. Weber, Iman Osman
Journal: Journal of Clinical Oncology (2023)

9523 Background: We previously reported the development of a machine learning algorithm to predict immunotherapy response in patients with advanced melanoma using retrospectively collected pretreatment histologic slides (Johannet et al, CCR 2021). In this study, we tested the validity of the same algorithm in two independent cohorts of melanoma patients enrolled in phase III clinical trials of immune checkpoint inhibitors (ICI), one metastatic, and one adjuvant. Methods: We examined 336 patients enrolled in CheckMate 067(NCT01844505) and CheckMate 238 (NCT02388906). We used deep convolutional neural networks (DCNN) to automatically segment images into three regions of interest: tumor, lymphocytes, and stroma. The algorithm was previously trained and tested to predict the complete and partial response (CR/PR) versus progression of disease (POD) and to predict the probability of progression-free survival (PFS) while on ICI. We tested the performance in the two cohorts; the first (CheckMate 067) included 164 patients with stage III/IV unresectable melanoma who received ipilimumab (n= 49), nivolumab (n = 59), or combination (n= 56) therapy as a first line, then tested whether the algorithm could perform as well in the second cohort (CheckMate 238) which included 172 patients with stage III/IV resectable melanoma who received adjuvant ipilimumab (n = 87) or nivolumab (n = 85) therapy as first line. Results: The segmentation classifier identified tumor within slides with an area under the curve (AUC) of 0.99. A combined model of DCCN and treatment predicted POD with an AUC of 0.72 in metastatic melanoma patients enrolled in Checkmate 067. The DCCN classified patients into high and low risk based on their likelihood of PFS (P &lt;0.0001). However, the same algorithm is not effective in predicting recurrence in patients treated in the adjuvant setting in Checkmate 238 (AUC 0.52). Retraining and testing using only patients treated in the adjuvant setting improved the AUC average to 0.65-0.70. Conclusions: Our results show the reproducibility of our previously developed algorithm in predicting response in patients with advanced metastatic melanoma. The inability of the model to predict recurrence in patients treated in the adjuvant setting might reflect the difference in the endpoint tested (response versus recurrence), which requires further training on larger datasets for this particular endpoint prediction, and/or the limited tumor volume in resected disease below a threshold that machine learning can predict a difference.
Response-adapted therapy for locally advanced nasopharyngeal carcinoma based on clinical response and circulating Epstein-Barr virus DNA level post induction chemotherapy.
Authors: Chaosu Hu, Xiaomin Ou
Journal: Journal of Clinical Oncology (2023)

TPS6112 Background: For locally advanced nasopharyngeal carcinoma (NPC), the mainstay treatment is cisplatin-based concurrent chemoradiation (CCRT). Recent phase III clinical trials have demonstrated that induction chemotherapy (ICT) plus CCRT, compared with CCRT alone, further improved progression-free survival (PFS). However, not every patient has good response to ICT. Evidence has accumulated that those with poor response to ICT, or those with detectable Epstein-Barr Virus (EBV) DNA post ICT, correlated with poorer PFS. In addition, real-time monitoring of plasma EBV DNA response adds prognostic information, and has the potential utility for risk-adapted treatment intensification in NPC. The aim of this study is to clarify whether response-adapted strategy based on clinical efficacy and EBV DNA response confers survival benefit to patients with locally advanced NPC. Methods: This is an open-label, 3-arm, phase II study. Patients with pathologically confirmed, locally advanced NPC (III-IVA, excluding T3N0M0, 8 th AJCC staging system), with pretreatment detectable plasma EBV DNA level and ECOS PS 0-1 were eligible. Patients will receive one cycle of GP-based ICT. After one cycle of ICT, plasma EBV DNA and head and neck MR are performed. Based on clinical efficacy (evaluated per RECIST 1.1 criteria) and changes of plasma EBV DNA after one cycle, patients will be divided into three arms. Patients with good response (Arm A: Early Responders, undetectable EBV DNA level and CR/PR) will directly receive CCRT. Patients with intermediate response (Arm B: Intermediate Responders, detectable EBV DNA and CR/PR/decreased SD; or undetectable EBV DNA yet without CR/PR) will be randomized to experiment subgroup (GP combined with Toripalimab for two additional cycles then CCRT and maintenance Toripalimab treatment) and standard subgroup (GP for two additional cycles then CCRT). Patients with poor response (Arm C: Treatment Resistant, increased EBV DNA level, or PD/enlarged SD) will be switched to TP regimen combined with Toripalimab, followed by CCRT and maintenance Toripalimab treatment. Sample size calculation is based on 2-year PFS rate for arm B as the primary endpoint (one-sided α = 0.10, power = 0.80). Our target sample size is estimated to be 198-240, among them 168 for arm B. Secondary endpoints include adverse events determined by CTCAE v5.0, ORR at 3 months post-CRT, 2-year locoregional recurrence-free survival (LRFS) rate, 2-year distant metastasis-free survival (DMFS) rate, 2-year overall survival (OS) rate, as well as quality of Life for arm B. Exploratory endpoints include 2-year PFS rate, LRFS rate, DMFS rate, OS rate, ORR at 3 months post-CRT, adverse effects, and quality of life for arm A and arm C. This trial opened to accrual in July 2022 and the recruitment is ongoing. Clinical trial information: NCT05628922 .